There are two types of nucleic acids, namely deoxyribonucleic acid ( DNA ) and ribonucleic acid ( RNA). Primarily, nucleic acids serve as repositories and transmitters of genetic information Brief history DNA was discovered in 1869 by Johann Friedrich Miescher, a Swiss researcher. The demonstration that DNA contained genetic information was first made in 1944, by Avery, Macleod and MacCary
Functions of nucleic acids : DNA is the chemical basis of heredity and may be regarded as the reserve bank of genetic information. DNA is exclusively responsible for maintaining the identity of different species of organisms over millions of years. Further, every aspect of cellular function is under the control of DNA. The DNA is organized into genes, the fundamental units of genetic information.
Components of nucleic acids: Nucleic acids are the polymers of nucleotides (polynucleotides) held by 3c and 5c phosphate bridges. nucleic acids are built up by the monomeric units—nucleotides (It may be recalled that protein is a polymer of amino acids).
NUCLEIC ACIDS Two Types: DNA (Deoxy Ribonucleic Acid) RNA (Ribonucleic Acid) Polymers of nucleotides (polynucleotides) held by 3' and 5' phosphate bridges Made up of monomeric units – nucleotides
Nucleotides Nucleotides are composed of a nitrogenous base, a pentose sugar and a phosphate. Nucleotides perform a wide variety of functions in the living cells, besides being the building blocks or monomeric units in the nucleic acid (DNA and RNA) structure. These include their role as structural components of some coenzymes of B-complex vitamins (e.g. FAD, NAD+), in the energy reactions of cells (ATP is the energy currency), and in the control of metabolic reactions.
COMPOSITION OF NUCLEOTIDES DNA: A,G,C,T RNA: A,G,C,U
what is difference between nucleoside and nucleotide STRUCTURE OF NUCLEOTIDES Sugar base NUCLEOSIDE sugar base NUCLEOTIDE p
NITROGENOUS BASES The nitrogenous bases found in nucleotides are aromatic heterocyclic compounds Two types: Purine Pyrimidine
Nitrogen base Purine ring Pyrimidine ring
purines
pyrimidine
Major purine Bases in Nucleic Acids Consists of a pyrimidine ring & imidazole ring fused together. Purines are numbered in the anti-clockwise direction
Major pyrimidine bases in nucleic acids Pyrimidines are numbered in clockwise DNA contains - C&T RNA contains - C&U
Other BIOLOGICAL IMPORTANT BASES Xanthine, Hypoxanthine are the intermediate products in purine degradation End product of purine degradation – Uric acid
SUGAR OF NUCLEIC ACIDS The 5c Monosaccharides (Aldo-pentose) are found in the nucleic acid RNA -- D-Ribose DNA -- D-deoxyribose Two sugars differ in structure at C 2 Deoxyribose has one oxygen less at C 2 compound to ribose
Nucleoside : base + sugar The sugar is linked to the heterocyclic base via a -N- glycosidic bond to N-1 of a Pyrimidine or N-9 of a Purine
How ribose sugar gets attached to nitrogenous base? H2O Adenylic acid adenine ribonucleotide
The names of purine nucleosides end in osine and the names of pyrimidine nucleosides end in -idine Nitrogenous base Ribonucleoside Deoxy ribonucleoside Adenine Adenosine (A) Deoxyadenosine (dA) Guanine Guanosine (G) Deoxyguanosine (dG) Thymine --- Deoxythymidine (dT) Uracil Uridine (U) --- Cytosine Cytidine (C) Deoxycytidine (dC)
Nucleotide : Nucleoside + Phosphate Nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar forms Mononucleotides
ADENOSINE NUCLEOTIDES Adenosine Mono Phosphate (AMP) Component of many coenzymes such as NAD + , NADP + , FAD, Coenzyme A Coenzymes are essential for the metabolism of carbohydrate, lipid and protein Adenosine Di Phosphate (ADP) Controls cellular respiration Muscle contraction
ADENOSINE NUCLEOTIDES Adenosine Tri Phosphate (ATP) Storage battery of the tissues Required as a source of energy in fatty acid synthesis, gluconeogenesis, cholesterol synthesis, protein synthesis Muscle contraction, nerve transmission
Cyclic AMP (c-AMP) Formed from ATP by the action of adenylate cyclase Acts as a second messenger for many hormones e.g. epinephrine, glucagon Enhances the degradation of storage fuels like fat and glycogen by stimulating lipolysis, glycogenolysis Inhibits the aggregation of blood platelets Increases the secretion of acid by the gastric mucosa
Cyclic AMP
Guanosine nucleotides Oxidation of Succinyl CoA to Succinate in the TCA cycle involves phosphorylation of Guanosine Di Phosphate (GDP) to form GTP Guanosine Tri Phosphate (GTP) Stimulation of adenylate cyclase enzyme Protein Synthesis
Guanosine nucleotides Cyclic Guanosine 3’5’-Monophosphate (c-GMP) formed from GTP by guanylyl cyclase intracellular signal or second messenger that can act antagonistically to c-AMP involved in smooth muscle relaxation and vasodilation
Uridine nucleotides Uridine Di Phosphate (UDP) Involved in glycogenesis UDP- glucose and UDP- galactose takes part in galactose metabolism and synthesis of lactose and cerebrosides UDP- glucuronic acid is required for detoxification and for synthesis of mucopolysaccharides
Cytidine nucleotides CTP & CDP are involved in the formation of phospholipids CDP- choline is involved in the synthesis of sphingomyelin
Miscellaneous PAPS( Phospho Adenosine Phospho Sulphate): Formed from ATP & SO 4 in liver Required for Biosynthesis of mucopolysaccharides Formation of Sulpholipids Conjugation of phenols, indole, ethereal SO 4
introduction Chemically synthesized analogues of Purines, Pyrimidines their nucleosides, and nucleotides have therapeutic applications in clinical medicine analogues Prepared either by altering the heterocyclic ring or sugar moiety Inhibits of specific enzymes essential for nucleic acid synthesis by the drug. Used chemotherapeutically to control cancer or infections
ANTI-METABOLITES CYTARABINE Chemotherapy of cancer & viral infection AZATHIOPURINE Immuno-Suppressive Agent (ISA) Used during organ transplantation
ANTI-METABOLITES AZIDOTHYMIDINE (AZT) Structural analogue of Thymidine, used in the treatment of AIDS Terminates DNA synthesis catalyzed by the reverse transcriptase of retroviruses such as HIV 5-Iododeoxyuridine Used in the treatment of herpetic keratitis (Infection of the cornea by herpers virus)
ANTI-METABOLITES Arabinosyl adenine Treatment of neurological disease, viral encephalitis Allopurinol Treatment of hyperuricaemia and Gout
Plants containing methylated purines Caffeine (1,3,7-tri methyl xanthine) Acts as a CNS stimulant, restores alertness reduces drowsiness Excess intake of caffeine causes Tachycardia (Increases heart rate) Increases the force & depth of respiration
Plants containing methylated purines Theobromine (3,7-Di methyl xanthine) Found in leaves of the tea leaves and chocolate Vasodilator, reduces blood pressure Increases heart rate & increases frequency of micturition Theophylline (1,3-Di methyl xanthine) Relaxes bronchial smooth muscle Increases heart rate, blood pressure & renal blood flow Stimulates the CNS Inhibits tubular reabsorption of Na + & Cl -
Overall Functions of nucleotides Building blocks or monomeric units of nucleic acid (DNA and RNA) Involved in the energy reactions of cell e.g. ATP Controls metabolic reactions Cyclic AMP and Cyclic GMP act as second messengers Carries of high energy intermediates in carbohydrate, lipid and protein metabolism